In this prospective, placebo-controlled study, we evaluated the effect of prophylactic ondansetron therapy on emergence agitation of children who underwent minor surgery below the umbilicus. Seventy children aged one to six years and American Society of Anesthesiologists physical status I were studied. Children were premedicated with midazolam rectally and were randomly assigned to receive either ondansetron (Group O) or placebo (Group P) in combination with caudal anaesthesia. Children in Group O received intravenous ondansetron (0.1 mg/kg for children weighing < 40 kg, 4 mg for children weighing > 40 kg) and Group P (n = 35) received normal saline 2 ml following anaesthesia induction with sevoflurane. Airway management was provided with LMA-Proseal without muscle relaxation and anaesthesia maintenance was provided with a 60:40 N2O:O2 mixture and sevoflurane. Emergence agitation was evaluated with a ten point scale and pain level was assessed every 10 minutes for the first 30 minutes after admission to the recovery room. There were no significant differences between the placebo and ondansetron groups with respect to demographic, anaesthetic and surgical details. Incidences of emergence agitation in ondansetron and placebo groups were similar (32.4% and 30.3% at 10 minutes respectively). Mean modified Children's Hospital of Eastern Ontario pain scale scores and mean ten-point scale scores and emergence agitation incidences decreased similarly after 10 minutes in both groups. Ready time for discharge was similar between the groups. Agitated patients had significantly increased ready time for discharge compared to non-agitated patients (P = 0.001). Prophylactic intravenous ondansetron administration does not reduce emergence agitation comparing to placebo after sevoflurane anaesthesia.